A 2-nitroimidazole derivative represented by the following formula (5) exhibits an action of promoting radiosensitivity of hypoxic cells existing in cancers. Because it has the excellent radiosensitivity and is highly safe, this compound is known to be useful as a drug used along with radiotherapy of cancer (Japanese Patent Application Laid-open (kokai) No. 223258/1991). ##STR2##
A process of the following reaction scheme is known for preparing the 2-nitroimidazole derivative (5). ##STR3##
This process comprises a step of selectively acylating three hydroxy groups, two primary hydroxy groups and one secondary hydroxy group, among four hydroxy groups in erythritol which is a raw material compound. It is essential to react erythritol at a low temperature in order to differentiate the reactivities of the primary hydroxy group and the secondary hydroxy group. But at such a low temperature, a large amount of solvent is required, because this raw material is scarcely soluble. Further, because the reaction product from this step is a mixture containing tetra-, tri-, di- and mono-acylated compounds, and unreacted compound, purification by column chromatography or the like is indispensable in order to selectively obtain the target triacylated compound. The low yield of this step results in the decrease in the overall yield of the process. In addition, expensive raw materials such as D-erythritol and L-erythritol must be used in order to produce the optically active 2-nitroimidazole derivative.
The 2-nitroimidazole derivative (5) has two asymmetric carbon atoms. Isolation of the optical isomers is so difficult that there have been no reports on the successful isolation of these isomers. Furthermore, nothing have been known at all about the pharmaceutical activities of these optical isomers.
An object of the present invention is therefore to provide optical isomers of 2-nitroimidazole derivative (5) and a drug comprising the same as an effective components.
Other objects of the present invention is to provide a novel process for the preparation of the 2-nitroimidazole derivative (5) and an intermediate for preparing this compound.